scholarly journals Alterations in mitochondrial function and cytosolic calcium induced by hyperglycemia are restored by mitochondrial transcription factor A in cardiomyocytes

2008 ◽  
Vol 295 (6) ◽  
pp. C1561-C1568 ◽  
Author(s):  
Jorge Suarez ◽  
Yong Hu ◽  
Ayako Makino ◽  
Eduardo Fricovsky ◽  
Hong Wang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mitochondrial Dna ◽  
High Glucose ◽  
Cytosolic Calcium ◽  
Neonatal Rat ◽  
Calcium Handling ◽  
Mitochondrial Transcription ◽  
Rat Cardiomyocytes ◽  
Mitochondrial Transcription Factor ◽  
Mitochondrial Transcription Factor A

Mitochondrial transcription factor A (TFAM) is essential for mitochondrial DNA transcription and replication. TFAM transcriptional activity is decreased in diabetic cardiomyopathy; however, the functional implications are unknown. We hypothesized that a reduced TFAM activity may be responsible for some of the alterations caused by hyperglycemia. Therefore, we investigated the effect of TFAM overexpression on hyperglycemia-induced cytosolic calcium handling and mitochondrial abnormalities. Neonatal rat cardiomyocytes were exposed to high glucose (30 mM) for 48 h, and we examined whether TFAM overexpression, by protecting mitochondrial DNA, could reestablish calcium fluxes and mitochondrial alterations toward normal. Our results shown that TFAM overexpression increased to more than twofold mitochondria copy number in cells treated either with normal (5.5 mM) or high glucose. ATP content was reduced by 30% and mitochondrial calcium decreased by 40% after high glucose. TFAM overexpression returned these parameters to even higher than control values. Calcium transients were prolonged by 70% after high glucose, which was associated with diminished sarco(endo)plasmic reticulum Ca2+-ATPase 2a and cytochrome- c oxidase subunit 1 expression. These parameters were returned to control values after TFAM overexpression. High glucose-induced protein oxidation was reduced by TFAM overexpression, indicating a reduction of the high glucose-induced oxidative stress. In addition, we found that TFAM activity can be modulated by O-linked β- N-acetylglucosamine glycosylation. In conclusion, TFAM overexpression protected cell function against the damage induced by high glucose in cardiomyocytes.

141 Mitochondrial transcription factor a mitochondrial DNA repair

Mitochondrion ◽  
2010 ◽  
Vol 10 (2) ◽  
pp. 240
Author(s):  
Deborah L. Croteau ◽  
Anne-Cécile V. Bayne ◽  
Chandrika Canugovi ◽  
Scott Maynard ◽  
Nadja de Souza-Pinto ◽  
...  
Keyword(s):  
Dna Repair ◽  
Transcription Factor ◽  
Mitochondrial Dna ◽  
Mitochondrial Transcription ◽  
Mitochondrial Transcription Factor ◽  
Mitochondrial Dna Repair ◽  
Mitochondrial Transcription Factor A

A human mitochondrial transcriptional activator can functionally replace a yeast mitochondrial HMG-box protein both in vivo and in vitro

1993 ◽  
Vol 13 (3) ◽  
pp. 1951-1961
Author(s):  
M A Parisi ◽  
B Xu ◽  
D A Clayton
Keyword(s):  
Transcription Factor ◽  
Mitochondrial Dna ◽  
Nuclear Gene ◽  
Transcriptional Activator ◽  
Yeast Mitochondria ◽  
Yeast Protein ◽  
Mitochondrial Transcription ◽  
Mitochondrial Transcription Factor ◽  
Mitochondrial Transcription Factor A

Human mitochondrial transcription factor A is a 25-kDa protein that binds immediately upstream of the two major mitochondrial promoters, thereby leading to correct and efficient initiation of transcription. Although the nature of yeast mitochondrial promoters is significantly different from that of human promoters, a potential functional homolog of the human transcriptional activator protein has been previously identified in yeast mitochondria. The importance of the yeast protein in yeast mitochondrial DNA function has been shown by inactivation of its nuclear gene (ABF2) in Saccharomyces cerevisiae cells resulting in loss of mitochondrial DNA. We report here that the nuclear gene for human mitochondrial transcription factor A can be stably expressed in yeast cells devoid of the yeast homolog protein. The human protein is imported efficiently into yeast mitochondria, is processed correctly, and rescues the loss-of-mitochondrial DNA phenotype in a yeast abf2 strain, thus functionally substituting for the yeast protein. Both human and yeast proteins affect yeast mitochondrial transcription initiation in vitro, suggesting that the two proteins may have a common role in this fundamental process.

scholarly journals Mitochondrial Transcription Factor A Regulates Mycobacterium bovis–Induced IFN-β Production by Modulating Mitochondrial DNA Replication in Macrophages

2019 ◽  
Author(s):  
Yinjuan Song ◽  
Tariq Hussain ◽  
Jie Wang ◽  
Yi Liao ◽  
Ruichao Yue ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mitochondrial Dna ◽  
Mycobacterium Bovis ◽  
Intracellular Survival ◽  
Vital Role ◽  
Mitochondrial Transcription ◽  
Host Immune Responses ◽  
Mitochondrial Transcription Factor ◽  
Copy Numbers ◽  
Mitochondrial Transcription Factor A

Abstract Background Mycobacterium bovis persistently survives in macrophages by developing multiple strategies to evade host immune responses, and the early induction of interferon-β (IFN-β) is one of these critical strategies. The mitochondrial transcription factor A (TFAM) plays a vital role in mitochondrial DNA (mtDNA) metabolism and has been suggested to influence IFN-β production in response to viral infection. However, its role in the production of IFN-β by M. bovis has not been elucidated. Methods In the current study, we investigated the role of TFAM in the production of IFN-β in M. bovis–infected macrophages. Results We found that knockdown of TFAM expression significantly reduced M. bovis–induced IFN-β production, mtDNA copy numbers and cytosolic mtDNA were increased in murine macrophages with M. bovis infection, cytosolic mtDNA contributed to IFN-β production, and TFAM was required for the increase in mtDNA copy numbers induced by M. bovis. We also observed that TFAM affected the intracellular survival of M. bovis. Conclusions Our results suggest that TFAM plays an essential role in M. bovis–induced IFN-β production by regulating mtDNA copy numbers. This might be a new strategy adopted by M. bovis for its intracellular survival.

Sign in / Sign up

Export Citation Format

Share Document